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Background Increasing intentions to quit e-cigarettes among youth and young adults can reduce usage rates by making quit attempts more likely. This study assessed the potential impacts of a national media campaign, focused on building knowledge of e-cigarette use risks and cessation resources, on intentions to quit and campaign-targeted beliefs about mental health and quitting. Methods A national sample from a repeated cross-sectional online survey was collected from March 2022 to August 2023, among youth and young adults who reported e-cigarette use in the past 30 days (N=5169). Regression models were used to assess associations between weekly campaign awareness and frequency of exposure on intentions to quit e-cigarette use within the next 6 months and targeted beliefs related to mental health and quitting. Results Participants who were aware of both cessation and knowledge-building messaging were more likely to report intentions to quit e-cigarette use in the next 6 months (OR 1.43, (95% CI 1.21, 1.69)) and agree with quitting-related targeted beliefs (ORs 1.351.63) and a mental health targeted belief scale (b=1.14 (95% CI 0.69, 1.59)), relative those with no messaging awareness. The frequency of exposure to cessation messaging held a dose-response relationship with almost all outcomes. Conclusion Findings suggest that frequency and awareness of messaging that educates about e-cigarette harms to mental health and about cessation resources are associated with higher quitting intentions among young people who use e-cigarettes.

Introduction: Informed consent (IC) plays a central role in medical care and research. Practices for endovascular thrombectomy (EVT) in acute stroke are not well elucidated. We investigated the clinical roles and medical specialties of individuals who obtain IC for EVT, aiming to provide insights for enhancing the process in contemporary stroke care. Methods: We conducted a survey from July to December 2023 among clinicians involved in acute stroke care. Utilizing Qualtrics, we disseminated a structured questionnaire through various national and international platforms including the American Academy of Neurology and StrokeNet. This analysis summarizes findings pertaining to the characteristics of those who obtain EVT IC at the respondents’ institution. Results: Among 168 participants, 71% were staff physicians, 70% practiced in the United States (US), and 70% were based at academic centers. The most common medical specialties obtaining EVT IC were neurology (77%), followed by neurosurgery (41%), radiology (30%) and emergency medicine (10%) ( Table 1 ). Staff physician (61%) was the most common clinical role involved, followed by fellows (43%), residents (48%), and advanced practice providers (APP, 36%) ( Table 2 ). Non-US institutions were more likely to utilize a provider from neurology alone (50% vs. 31%, p=0.016) and staff physicians (76% vs. 54%, p=0.008), while US institutions were more likely to utilize providers from neurosurgery (51% vs. 18%, p<0.001), APPs (43 vs. 18%, p=0.002) and residents (56% vs. 28%, p=0.001). Non-academic institutions more frequently used emergency medicine providers (25% vs. 5%, p<0.001) and APPs (50% vs. 31%, p=0.031), while academic institutions commonly utilized neurosurgery providers (48% vs. 18%, p=0.001), residents (59% vs. 13%, p<0.001) and fellows (52% vs. 18%, p<0.001). Conclusion: This study highlights the diverse medical specialties and clinical roles of persons obtaining IC for EVT, with neurologists and staff physicians being the most frequently utilized. These variations likely reflect availability and capacity of certain providers in different settings. Future efforts to optimize the IC process should be multi-disciplinary, with standardized content that addresses issues such as ischemic core volume, outcome expectations and diversity.

Introduction: Extracranial carotid artery pathology accounts for 15-20% of ischemic strokes. Advancements in magnetic resonance angiography (MRA) with vessel wall imaging (VWI) have enabled the identification of vulnerable plaques, aiding in risk stratification for neurovascular events. This pilot study aimed to identify proteins in plaques with and without vulnerable features on MRA with VWI. Hypothesis: There is a differential proteomic profile of vulnerable and non-vulnerable, thus, these can serve as potential biomarkers for disease progression, stroke prevention, and therapeutic targets. Methods: Consecutive patients undergoing carotid endarterectomy (CEA) were included in the study cohort with pre-operative MRA with VWI. A retrospective chart review was conducted to extract pertinent clinical data including cardiovascular risk factors and medications. The proteomic analysis involved Tandem Mass Tag (TMTpro) labeling of peptides, basic pH HPLC fractionation, and NanoLC-tandem mass spectrometry. Results: A total of sixteen plaques were retrieved from fifteen patients. There were 73.3% male patients. The most common comorbidities were hyperlipidemia (93.3%) and hypertension (80%). 31.2% of patients had symptomatic disease. Eleven plaques were vulnerable in preoperative MRI with VWI. From those, intraplaque hemorrhage was the most common feature (81.1%) . Proteomic analysis revealed 23 relevant proteins significantly elevated in vulnerable plaques, including Proteinase 3 (PRTN3), Phospholipid Transfer Protein (PLTP), and S100 Calcium-Binding Protein A12 (S100A12), with increased abundance exceeding two-fold changes or above (P<0.001). Conversely, three proteins exhibited reduced abundance in vulnerable plaques including Dynamin-3 (DNM3), Transmembrane Protein 181 (TMEM181), and Adducin-3 (ADD3) (P<0.05). All results are summarized in Figure 1A-C and Table I and II. Conclusion: This study contributes to the understanding of protein biomarkers associated with carotid plaque vulnerability, offering insights into disease progression, stroke prevention, and identification of potential therapeutic targets (Figure 1D) . Furthermore, these patients could benefit from early surgical intervention if these biomarkers were to be detected. We present a comprehensive study of multiple proteins with significant bioavailability in explanted plaque specimens that can serve as a foundation for identifying blood biomarkers for future validation studies.

Background: Carotid stenosis has been associated with stroke and cognitive impairment. It remains unclear if hypometablism, a marker for neurodegeneration, may be in the mechanistic pathway in the association between carotid stenosis and cognitive decline. This study aims to investigate whether patients with carotid stenosis exhibit reduced cerebral glucose metabolism, using 18-FDG PET imaging as a sensitive measure of brain’s glucose metabolism. Methods: We have identified 138 patients from one health care system who underwent 18-FDG PET imaging and had extracranial carotid imaging (doppler ultrasound/CT angiography/MR angiography) within 1 year of PET scan. Severity of carotid stenosis was defined using NASCET criteria as <50% (mild), 50-69% (moderate), >70% (high-grade). Cerebral glucose metabolism was quantified by measuring standardized uptake value ratio (SUVR) after normalizing to pons in 12 different regions of interest (ROI). Hypometabolism was defined using the cutoff of SUVR <1.41. SUVR and hypometabolism measures were compared across severity of carotid stenosis. Results: Of 138 patients identified, 54 were excluded due to indeterminant ipsilateral hemisphere status. Mild, moderate and severe stenosis was present in 86.9%, 4.8%, 8.3%, respectively. The analysis revealed a numerically reduced cerebral glucose metabolism in patients with moderate to severe carotid stenosis compared to control subjects (Table 1). The most pronounced decrease in FDG uptake was observed in regions supplied by the affected carotid artery, particularly the ipsilateral cortical areas. There was a numerically increased risk of hypometabolism with increasing carotid stenosis: Adjusted odds of hypometabolism ipsilateral to the carotid stenosis were 2.90, 5.56 across patients with moderate and high-grade carotid stenosis in sensorimotor cortex (trend-P=0.095). These findings were consistent across different regions supplied by the stenotic carotid artery but attenuated in territories supplied by unaffected posterior arteries (Table 2). Conclusions: FDG-PET imaging demonstrates reduced glucose metabolism in patients with carotid stenosis, suggesting that cerebral hypoperfusion may contribute to the metabolic disturbances observed in these patients. These results underscore the importance of early detection and management of carotid stenosis to mitigate potential cerebral metabolic deficits and the associated risk of dementia and ischemic stroke.

Introduction: The lack of understanding about the genetic and molecular basis of young stroke (<55 years of age) has hindered development of diagnostic, management, and therapeutic approaches. Whole exome sequencing (WES) can be leveraged as a tool for studying etiological processes underlying stroke. At the time of study inception, this is the single largest WES study in this unique young stroke population to uncover elusive stroke etiologies. Methods: The Mayo Clinic TAPESTRY database is a research program conducting whole exome sequencing of 100,000 participants. Of these, 406 participants met the criteria for young stroke (18-54 years of age) based on ICD-9 and ICD-10 diagnostic codes. Controls were TAPESTRY participants without a stroke-related ICD diagnosis. Cases were matched for age, gender, and race for a 1:4 case-control ratio. Ischemic stroke etiology was classified using TOAST classification. To uncover genetic mechanisms, a gene centric approach was used to identify variants in our cohort. A list of 66 genes known to be associated with young stroke was curated based on existing genetic databases. Various filtration strategies were used to identify potentially damaging variants (graphic 1). Results: There were 406 cases (363 ischemic and 43 hemorrhagic; 291 female; age at stroke onset 39.8±10.4; 368 were White) and 3,857 controls. TOAST classification yielded 20 patients with large artery atherosclerosis, 58 cardioembolic, 10 small vessel disease, 148 other determined (58 patent foramen ovale, 50 dissection, 48 hypercoagulable state, 11 Moyamoya, 11 vasculitis, 10 fibromuscular dysplasia), and 165 undetermined etiologies. Several individuals had multiple competing etiologies. Of cerebral hemorrhages, there were 6 aneurysmal, 6 arteriovenous malformation, 5 hypertensive, 2 substance abuse, 3 trauma, and 21 other etiologies. Across the entire cohort, 35,054 variants were found within the 66 genes identified from the literature. Filtration identified 48 potentially damaging variants across 30 genes in 44 patients (20 cryptogenic and 21 other: 12 patent foramen ovale, 5 vasculitis, 4 dissection, 4 cardioembolic) that were absent in controls. Conclusion: WES is a powerful tool that can be used to uncover potential genetic mechanisms in the young stroke population. An improved understanding of etiologies would improve diagnostics and pave the way for new preventive and therapeutic approaches, thus improving the overall care of young stroke patients.

Abstract Background The COVID-19 pandemic has underscored challenges with patient adherence to medical directives, particularly vaccine acceptance. While sociodemographic factors have been linked to non-COVID-19 vaccine hesitancy, the relationships between patient experience, the COVID-19 pandemic, and adherence to routine vaccinations are uncertain.Figure 1:Yearly influenza vaccine refusal, influenza vaccine administrations, and overall patient satisfaction since establishing care with a primary care provider from 2017-2023.Panel A (Influenza Refusals): the number of vaccine refusals among individuals who are Intermittently Vaccinated and Never Vaccinated for seasonal influenza since establishing care with a primary care provider over time.Panel B (Influenza Vaccinations): the number of vaccines administered over time since establishing care with a primary care provider among those who are Always Vaccinated and Intermittently Vaccinated for seasonal influenza.Panel C (Overall Satisfaction): the number of patients who indicated that they were maximally satisfied with their overall care following any interaction with the healthcare system over time. Methods We retrospectively analyzed influenza vaccination records of adult primary care patients in Olmsted County, Minnesota. Vaccination history was examined during two phases: Pre-Pandemic (1/1/2017—2/28/2020) and Pandemic-Plus (3/1/2020—12/31/2023). Vaccination status was defined as “always vaccinated” (AV), “never vaccinated” (NV), or “intermittently missed years of vaccinations” (IV) for seasonal influenza. Patient dissatisfaction was determined if patients negatively ranked their overall quality of care on standard patient experience surveys. We explored the relationship between influenza vaccination rates, healthcare engagement, and patient satisfaction.Figure 2:Multinomial logistic regression of patient satisfaction on vaccination status across the phases of the COVID-19 Pandemic, adjusted for engagement in the health care system, participation, and area of deprivation index (ADI) for patients that were (A) intermittently vaccinated compared to always vaccinated and (B) never vaccinated comparted to always vaccinated. The “Pre-pandemic phase” refers to influenza immunization data and patient satisfaction data prior to March 2020. The “Pandemic-plus phase” refers to immunization data and patient satisfaction data from March 2020 to January 2024. Low ADI ranking refers to areas with a low level of deprivation, whereas high ADI ranking refers to areas with a high level of deprivation. Individuals were considered low if they came from an area with a state ADI ranking from 1 to 5 and were considered high if they came from an area with a state ADI ranking from 6 to 10. Results From 1/1/2017 to 12/31/2023, 21% of individuals were AV (n=36,632), 52% were IV (n=90,776), and 27% were NV (n=46,418) for seasonal influenza. Post-pandemic onset, 7% (n=3,556) of the Pre-Pandemic AV and 32% (n=16,710) of the Pre-Pandemic IV never received another influenza vaccine. In the Pandemic-Plus phase, the IV and NV had a higher likelihood of disengagement with the healthcare system [odds ratio (OR) (95% CI): 1.59 (1.55, 1.64); 4.21 (4.09, 4.33)], residing in areas of greater deprivation [1.58 (1.53, 1.62); 1.99 (1.94, 2.05)], and self-identifying their race as Black [2.29 (2.09, 2.51); 3.29 (3.01, 3.60)] compared to the AV. After adjusting for healthcare engagement and area of deprivation, dissatisfaction OR increased from 1.03 (0.99,1.07) Pre-Pandemic to 1.07 (1.03,1.12) in the Pandemic-Plus phase among IV compared to AV. Similarly, the OR of dissatisfaction rose from 1.11 (1.05, 1.18) Pre-Pandemic to 1.16 (1.09, 1.24) in the Pandemic-Plus phase among those who were NV compared to those AV. Conclusion Higher healthcare dissatisfaction was observed among those inconsistently adherent to vaccination recommendations. Targeted efforts to enhance patient satisfaction may boost vaccination rates. Disclosures All Authors: No reported disclosures

Background. Early allograft dysfunction (EAD) affects outcomes in liver transplantation (LT). Existing risk models developed for deceased-donor LT depend on posttransplant factors and fall short in living-donor LT (LDLT), where pretransplant evaluations are crucial for preventing EAD and justifying the donor’s risks. Methods. This retrospective study analyzed data from 2944 adult patients who underwent LDLT at 17 centers between 2016 and 2020. We developed a logistic regression model to predict EAD based on this development cohort. We used data from 1020 patients at the King Faisal Transplant Center for external validation. Results. In the development cohort, 321 patients (10.9%) experienced EAD. These patients had poorer health status, more liver decompensation, and higher requirements of hospitalization than those without EAD. Multivariable logistic regression identified independent pretransplant predictors of EAD: laboratory Model for End-Stage Liver Disease score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.06-1.09), the necessity for hospitalization at the time of transplant (OR, 2.58; 95% CI, 2.00-3.30), and graft weight in kilogram (OR, 0.27; 95% CI, 0.17-0.45). Using these predictors, we developed the model for EAD after LDLT, which demonstrated strong discriminative ability in the development cohort with an area under the curve (AUC) of 0.71 (95% CI, 0.68-0.74). The model maintained high discrimination during internal validation (AUC, 0.70; 95% CI, 0.67-0.73) and showed a modest reduction in discriminative power in external validation (AUC, 0.65; 95% CI, 0.61-0.68). Conclusions. EAD post-LDLT is influenced by the recipient’s pretransplant health condition and the graft weight. Integrating the model for EAD after LDLT into the pretransplant process of pairing donors and recipients can enhance the safety and efficacy of LDLT.

566 Background: Immune checkpoint inhibitors (ICIs) have become the preferred treatment for unresectable hepatocellular carcinoma (HCC). Conflicting data exist regarding the prognostic value of immune-related adverse events (irAEs) in these patients. We aimed to explore potential the association between irAEs and prognosis in HCC patients treated with ICIs. Methods: We searched PubMed, Scopus, Web of Science, and CENTRAL databases for articles published from inception to June 2024 using keywords including ICI, HCC, and irAEs. Two reviewers independently screened studies for eligibility and relevant data. A random effects model was used for statistical analysis, and subgroup analysis was performed by the grade of irAEs. Results: Of 3,028 studies, 25 (n=4,116 patients) met criteria for inclusion. Atezolizumab plus bevacizumab was the most common treatment regimen (n=10 studies). About half (49.5%) of patients experienced irAEs. irAEs were associated with increased objective response rate (ORR) (pooled OR: 1.72; 95% CI: 1.36 – 2.19, I 2 =39%), higher complete response rate (pooled OR: 1.45; 95% CI: 1.21-1.74, I 2 =74%), and longer progression-free survival (PFS) (pooled HR: 0.66; 95% CI: 0.52-0.84, I 2 =71%). Although irAEs were associated with longer overall survival, this difference was not statistically significant (pooled HR: 0.83; 95% CI: 0.62 – 1.11, I 2 =73%). Subgroup analysis showed a survival benefit for patients with grade 1-2 irAEs (pooled HR: 0.50; 95% CI: 0.36-0.67, I 2 =0%) but not for those with grade 3-4 irAEs (pooled HR: 0.95; 95% CI: 0.24-3.72, I 2 =84%). Conclusions: The development of irAEs is associated with a favorable prognosis in HCC, including improved PFS and higher ORR. A survival benefit was noted in patients with mild irAEs, but not in those with severe irAEs. Future studies are needed to determine if a differential survival benefit relates to the continuation vs. discontinuation of ICI therapy.

Abstract Background Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) and is available in subcutaneous (SC) formulation. This analysis assessed the long-term safety outcomes of specific interest to the SC formulation of VDZ. Methods Patients (pts) who participated in VISIBLE 1 or VISIBLE 2 were eligible to enrol in VISIBLE OLE (NCT02620046). In VISIBLE 1, pts with UC were treated with placebo, VDZ SC or VDZ intravenous (IV). In VISIBLE 2, pts with CD were treated with placebo or VDZ SC. In VISIBLE OLE, pts received VDZ SC 108mg every 2 weeks (Q2W) or weekly. Pts received training on SC administration, and most injections were conducted at home by pt or caregiver. Safety of VDZ SC included assessing anti-VDZ antibody (AVA) status and injection site reaction (ISR) adverse events. Blood specimens for AVA assessment were collected 30 minutes before dosing every 16 weeks, at the final dose and the final safety visit 18 weeks after last dose. Data were assessed by treatment pts received during VISIBLE 1 and 2. Results Overall, 288 pts with UC and 458 pts with CD enrolled in VISIBLE OLE. A mean of 91.1 and 74.2 SC injections were completed by pts with UC and CD, respectively, during the OLE. Among pts with UC, the positive AVA rate was higher in pts previously treated with placebo (17.3%) than those treated with VDZ SC (3.4%) or IV (2.6%) (Table 1). The positive AVA rate was also higher among pts with CD previously treated with placebo (11.4%) than with VDZ SC (1.8%). A total of 14/288 pts (4.9%) with UC reported ISRs (Table 2), most of which were mild and none were serious. Two pts developed moderate ISRs; neither required dose modification and both were resolved. Overall, 19/458 pts (4.1%) with CD reported ISRs (Table 2). The majority of ISRs were mild, 2 were moderate and none were severe, and none required dose modification. No direct correlation between AVA status and ISRs was identified, with 11/14 pts (78.6%) with UC and 17/19 pts (89.5%) with CD who reported ISRs being AVA negative. All 5 pts who were AVA positive and reported an ISR had previously received placebo. The highest rate of ISRs were in pts who received placebo in VISIBLE 1 (13.5%). Conclusion No new long-term safety events were identified with the VDZ SC route of administration compared to IV, except for ISRs. A higher proportion of patients who had previously been treated with placebo than those treated with VDZ during VISIBLE 1 and 2 were AVA positive during VISIBLE OLE, supporting a benefit of continued therapy with VDZ SC after IV induction, rather than cessation of treatment for a period of time.

Abstract Background Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderate to severe ulcerative colitis (UC) or Crohn’s disease (CD). The subcutaneous (SC) formulation of VDZ was evaluated during the Phase 3 VISIBLE 1 and 2 studies. We report the long-term efficacy among patients (pts) with UC or CD treated with VDZ SC in the VISIBLE open-label extension (OLE) study. Methods Pts with UC or CD in VISIBLE 1/2 could enrol in VISIBLE OLE (NCT02620046). Pts in VISIBLE 1/2 who completed 52 weeks(W) of treatment with VDZ or placebo (randomised completers) and pts without clinical response at W6 who responded at W14 (non-randomised responders) received VDZ SC 108mg every 2W (Q2W) in the OLE. Pts with worsening disease were escalated to QW dosing. Clinical remission (partial Mayo score ≤2, no subscore &gt;1 in UC; HBI score ≤4 in CD) up to W168 was assessed (pts with missing data or escalated to QW dosing were imputed as non-response, irrespective of clinical status). The number of pts who regained clinical response when escalated to QW dosing was also assessed. Results were summarized by prior VISIBLE 1/2 treatment groups. Results Data from 231 pts with UC and 344 pts with CD were included. In pts with UC, baseline OLE clinical remission rates were 55.0%, 91.3% and 77.1% among randomised completers (N=124) previously treated with placebo, VDZ SC and VDZ IV in VISIBLE 1, respectively. At W168, 40.0%, 56.5% and 62.9%, respectively, were in clinical remission on Q2W dosing. In non-randomised responders with UC (N=107), 57.0% were in clinical remission at baseline and 29.9% at W168 (Figure). In pts with CD, baseline OLE clinical remission rates were 60.3% and 62.0% among randomised completers (N=226) previously treated with placebo and VDZ SC in VISIBLE 2. At W168, 32.4% and 37.3% were in clinical remission on Q2W dosing. In non-randomised responders with CD (N=118), 57.6% were in clinical remission at baseline and 27.1% at W168 (Figure). In pts with UC escalated to QW dosing, 22.2% and 38.1% achieved clinical remission and response at W8 after transitioning to QW. Among pts with CD escalated to QW dosing, 38.6% and 53.5% achieved clinical remission and response by W8 after transitioning to QW. Higher rates of remission and response were noted in VDZ completers than non-randomised responders. No new long-term safety signals were noted with VDZ SC vs IV, except for injection site reactions. Conclusion The clinical benefit of VDZ SC was maintained long-term during VISIBLE OLE. A subset of pts who escalated to QW dosing regained response. Findings support VDZ SC as a treatment option for patients with UC or CD who require long-term maintenance therapy.